Novel mutations associated with Carnitine-Acylcarnitine Translocase and Carnitine Palmitoyl Transferase 2 deficiencies in Malaysia

Abstract Objective Carnitine-acylcarnitine Translocase (CACT) deficiency; OMIM 212138 and carnitine palmitoyl transferase 2 (CPT2) deficiency; OMIM 600649 are rare inherited disorders of mitochondrial long chain fatty acid oxidation. The aim of our study is to review the clinical, biochemical and molecular characteristics in children diagnosed with CACT and CPT2 deficiencies in Malaysia. Design and Methods: This is a retrospective study. We reviewed medical records of six patients diagnosed with CACT and CPT2 deficiencies. They were identified from a selective high-risk screening of 50,579 patients from January 2010 until Jun 2020. Results All six patients had either elevation of the long chain acylcarnitines and/or an elevated (C16+C18:1)/C2 acylcarnitine ratio. SLC25A20 gene sequencing of patient 1 and 6 showed a homozygous splice site mutation at c.199-10T>G in intron 2. Two novel mutations at c.109C>T p. (Arg37*) in exon 2 and at c.706C>T p. (Arg236*) in exon 7 of SLC25A20 gene were found in patient 2. Patient 3 and 4 (siblings) exhibited a compound heterozygous mutation at c.638A>G p. (Asp213Gly) and novel mutation c.1073T>G p. (Leu358Arg) in exon 4 of CPT2 gene. A significant combined prevalence at 0.01% of CACT and CPT2 deficiencies was found in the symptomatic Malaysian patients. Conclusions The use of the (C16+C18:1)/C2 acylcarnitine ratio in dried blood spot in our experience improves the diagnostic specificity for CACT/CPT2 deficiencies over long chain acylcarnitine (C16 and C18:1) alone. DNA sequencing for both genes aids in confirming the diagnosis.